A Pilot Study Examining Diet in Primary Sclerosing Cholangitis (DINER)

A Pilot Study Examining a Vegan/Low-Sulfur Diet Versus the Specific Carbohydrate Diet in Patients With Primary Sclerosing Cholangitis

This research study is exploring the effects of dietary intervention in PSC. Study participants will be randomly assigned to either the Specific Carbohydrate Diet (SCD) or a vegan/low-sulfur diet for 8 weeks; the entire study will last approximately 14 weeks. Participants will work with BWH Registered Dieticians and receive dietary educational materials, recipes, and a food procurement stipend to support the new diet. Subjects will attend 7 video visits and have regular lab tests performed, requiring blood and stool samples.

Study Overview

• Status: Unknown
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Other: Dietary Intervention

Detailed Description

The chronic, autoimmune liver disease Primary Sclerosing Cholangitis (PSC) is a progressive cholestatic, hepatobiliary disease characterized by inflammation and fibrosis of the bile duct. As the disease progresses, it may result in debilitating bile duct cirrhosis, malignancy, and liver failure. Although the list of drugs studied for the treatment of PSC is extensive, the main, and commonly only, treatment option remains liver transplantation. Dietary manipulation is an approach of high interest to patients. Presumably, diet may have some influence on the intestinal microbiome and have a modifying impact on the diseases but this has not been well established.

The investigators propose a study period of approximately 14 weeks to evaluate the effects of the SCD and vegan/low-sulfur diet on the intestinal microbiome and bile acid composition in stool and serum. Patients will visit their study site or participate in a video visit 7 times over the course of the study. At the screening visit (Week 0), eligibility will be assessed, lab tests will be performed, and subjects will be randomized to dietary instruction on one of the two diets with educational materials, recipes, and food procurement stipend provided. Consent will be signed at or before the screening visit either in-person or remotely. Patients will be asked to collect a stool sample and complete a Food Frequency Questionnaire (FFQ).

The treatment phase of 8 weeks will begin at the baseline visit (Week 2). At each of the four time points during the treatment phase (Week 4, 6, 8, 10), participants will record in real-time what they eat by a smartphone app for 3-days, one of which includes a weekend. To enhance compliance to the intervention protocol, the dedicated study coordinator along with the Registered Dietitian will review the food diary data in real-time and discuss any challenges to comply with the meal intervention. After the 8-week treatment period is complete, patients will be encouraged to continue with their diet, self-directed, for 4 weeks following the end of the treatment phase (Week 10). Subjects will be asked to return for one final visit at Week 14 to complete a 3-day food diary and have labs drawn.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nadine Javier; Phone Number: 617-732-9481; Email: njavier@bwh.harvard.edu
• Study Contact Backup: Name: Gila Sasson, MD; Phone Number: 617-732-9481; Email: gsasson@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Nadine Javier; Phone Number: 617-732-9481; Email: njavier@bwh.harvard.edu
      • Contact: Fernanda Quevedo; Phone Number: 617-732-9173; Email: sfernandaquevedo@bwh.harvard.edu
      • Principal Investigator: Joshua Korzenik, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females between 18 and 70 years of age, inclusive based on the date of the screening visit
2. Willing and able to give informed consent prior to any study specific procedures being performed
3. Diagnosis of PSC documented by typical cholangiogram findings with no evidence of a secondary cause of sclerosing cholangitis
4. Serum alkaline phosphatase greater than 1.5 times the upper limit of the normal (ULN) reference range
5. Simple clinical colitis activity index < 5
6. For subjects on UDCA, the dose of UDCA must have been stable for at least 3 months before screening. For subjects not on UDCA, no UDCA use for at least 3 months before screening.
7. Platelet count > 150,000/mm3
8. Albumin > 3.3 g/dL
9. Serum creatinine < ULN
10. Willing and able to comply with scheduled visits, laboratory tests, stool collection, and other study procedures including to follow a vegan/low-sulfur diet or SCD for the duration of the trial regardless of treatment arm randomization
11. Able to read English and complete PSC PRO independently

Exclusion Criteria:

1. Pregnant or lactating females
2. ALT > 10 x ULN
3. Total bilirubin > 2 X ULN
4. INR > 1.2
5. Decompensated cirrhosis defined by ascites, hepatic encephalopathy, or variceal bleeding
6. Small duct PSC
7. Other causes of liver disease including secondary sclerosing cholangitis, viral, metabolic, alcoholic, and other autoimmune liver diseases. Subjects with non-alcoholic fatty liver disease may be included if there is no evidence of NASH in the opinion of the investigator
8. Positive AMA
9. History of liver transplantation
10. History of hepatocellular carcinoma or cholangiocarcinoma
11. Ascending cholangitis within 90 days of enrollment
12. Any antibiotic use within 90 days of enrollment or planned antibiotic use during the study period
13. Current vegetarian or adherence to the SCD
14. Nut allergy (Many of the recipes included in the specific carbohydrate diet substitute nut flour for wheat flour. Subjects randomized to either the specific carbohydrate diet arm will have difficulty with dietary adherence as they will be intolerant of this dietary staple).
15. Inability to complete dietary log.
16. History of malignancy within 5 years except for adequately treated carcinoma in situ of the cervix and basal or squamous cell carcinoma.
17. Concurrent participation in another therapeutic clinical trial
18. Celiac disease
19. Any laboratory abnormality or condition which in the opinion of the investigator could adversely affect the safety of the participant or impair the assessment of the study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Protein/Vegan/Low-Sulfur Diet; This is a specific diet that is both vegan and low in protein. The vegan diet eliminates all animal products, (including meats, eggs, dairy products) and animal by-products such as honey.	Other: Dietary Intervention; Subjects will be placed on 1 of 2 diets for a treatment period of 8 weeks with the support of dietitians; it will then be evaluated whether they can continue this diet on their own for 4 weeks.
Experimental: Specific Carbohydrate Diet; The Specific Carbohydrate Diet emphasizes consumption of specific carbohydrates that require minimal digestion. Therefore, it eliminates most carbohydrates, including grains, starches, dairy and sugars. The idea behind this diet is that it reshapes the microbiome of the intestines. The diet restricts the intake of certain carbohydrates that may increase the growth of "bad" bacteria possibly contributing to inflammation. By restricting the amount of these carbohydrates in the microbiome, the diet aims to reduce their activity in the gut and reduce inflammation.	Other: Dietary Intervention; Subjects will be placed on 1 of 2 diets for a treatment period of 8 weeks with the support of dietitians; it will then be evaluated whether they can continue this diet on their own for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shannon index	The primary endpoint will be the within group change in the Shannon diversity index. The Shannon diversity index is used to characterize species diversity in a community (the diversity in the fecal microbiome).	Control period (Weeks 0-2) to Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALP level	The investigators will be evaluating the trend of alkaline phosphatase reduction (U/L).	Control period (Weeks 0-2) to Week 14

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Massachusetts General Hospital; University of California, Davis
• Investigators: Principal Investigator: Joshua Korzenik, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Anticipated): August 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Diet; Specific Carbohydrate Diet; Primary Sclerosing Cholangitis; Low-Protein; Low-Sulfur; Vegan
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: 2019P002075

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No